The Preiss-Handler Pathway comprised the following sequence:
1. Nicotinic Acid+phosphoribosylpyrophosphate=Nicotinic Acid Mononucleotide (NaMN)+Pyrophosphate.
2. Nicotinic Acid Mononucleotide+ATP=Nicotinic Acid Adenine Dinucleotide (NaAD)+Pyrophosphate.
3. Nicotinic Acid Adenine Dinucleotide+Glutamine+ATP=Nicotinamide Adenine Dinucleotide (NAD)+Glutamate+AMP+Pyrophosphate.
4. Nicotinamide Adenine Dinucleotide+ATP=Nicotinamide Adenine Dinucleotide Phosphate (NADP)+ADP.
Nicotinic acid metabolism to nicotinic acid mononucleotide, NAD, and NADP (the Preiss-Handler Pathway) had been assessed in the human blood platelet, platelet lysate, the human red blood cell, and the rat liver slice.
In the early 1970's, Hoffman-LaRoche chemists synthesized several analogues of nicotinic acid in an effort to maximize antilipemic activity and minimize side effects. These and other analogues of nicotinic acid were assessed as inhibitors of the Preiss-Handler Pathway along with non-steroidal antiinflamatory drugs (NSAIDs)--especially salicylate and aspirin.
In 1991 and 1993, reports appeared in the New England Journal of Medicine and Cancer Research which indicated that the administration of aspirin, increased survival time of cancer patients.
Possibly, the mechanism was inhibition of the first reaction in the pathway of Preiss and Handler. Such inhibition could decrease the cellular levels of NAD and NADP, which are the first proton and electron carriers for energy production in virtually all cells.